The mononitration of amino-substituted aromatic compounds is of industrial importance since it provides a method of producing nitroanilines which are, inter alia, important intermediate compounds in the synthesis of dyes, antioxidants and especially pharmaceuticals. The mononitration of aniline derivatives in the ortho-position is of particular importance since the resulting 1,2-nitroanilines can be further reacted to form aromatic heterocycles with two hetero-nitrogen atoms, such as benzimidazoles.
Unfortunately, however, nitration of aromatic compounds on an industrial scale presents various problems.
Thus, the desired products are not usually obtainable in isomerically pure form since the isomeric equilibrium can only be influenced by the reaction conditions to a limited extent, as is well known, during the mononitration of differently substituted aromatic compounds (cf. for example the industrial mononitration of toluene: K. Weissermehl, H.-J. Arpe, Industrielle organische Chemie, 3rd Edition page 400-401). The separation of the desired regioisomer frequently proves very difficult. However, for industrial synthesis of pharmaceuticals, it is essential to be able to obtain extremely pure products in the individual reaction steps.
Another problem with nitration on an industrial scale is the safety risk, which is sometimes considerable. Thus, on the one hand, the reaction solutions required for the nitration of aromatic compounds are usually highly explosive, particularly when concentrated nitric acid is used as the nitrating agent. The reaction process is particularly dangerous when the accumulation of reaction compounds is very great. In such cases the individual reactants do not react immediately when combined but after a certain time delay. As a result, continuous and hence controlled conduct of the reaction is made difficult and the risk of a spontaneous explosive reaction increases. Another safety risk which is hard to calculate is presented by the products which are produced by the reaction. Di- and tri-nitrated by-products are particularly risky in this respect. The latter may in some cases be produced spontaneously in industrial-scale nitration processes, so that they are outside the control of those responsible for the process.